The purpose of this research project is to study the effect of hyperthermia given alone or in combination with radiation on experimental animal tumors. Tumor response will be studied in vivo by determining the dose-cell survival relationship, tumor growth delay and tumor control dose. To evaluate therapeutic gain, normal tissue response will be studied by scoring early and late foot reactions. Experimental animals will be specific pathogen free C3Hf/Sed mice derived from our defined flora colonies. A fibrosarcoma which arose spontaneously in a C3Hf/Sed will be used in most experiments. It is well-known that tumors contain a fraction of hypoxic cells which are radio-resistant and thus critical for radiotherapy. On the other hand, reoxygenation has been demonstrated in many animal tumors during fractionated radiotherapy. Therefore, it is important for cancer treatments to study changes of size of the hypoxic cell fraction during treatments as well as to establish an effective treatment modality which can inactivate clonogenic hypoxic cells. Recent studies have demonstrated that hypoxic cells are at least as sensitive to hyperthermia as aerobic cells and that thermal sensitivity increases at reduced pH levels. Therefore, we will extensively study 1) the effectiveness of hyperthermia in the inactivation of hypoxic tumor cells and the changes in the size of such cell fractions following treatment and 2) the effect of reduced pH on the response of tumor and normal tissues to hyperthermia. An effort will be made to establish an effective method to reduce blood and subsequently tumor tissue pH. In addition, thermal sensitivity of various histological types of tumors which arose spontaneously in our C3Hf/Sed mice will be studied. Data from these studies will be of practical value in planning clinical trials of treatment of cancer.